Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b

Chung I. Chang; Bing E. Xu; Radha Akella; Melanie H. Cobb; Elizabeth J. Goldsmith

doi:10.1016/S1097-2765(02)00525-7

Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b

Chung I. Chang, Bing E. Xu, Radha Akella, Melanie H. Cobb, Elizabeth J. Goldsmith

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280 Scopus citations

Abstract

The structures of the MAP kinase p38 in complex with docking site peptides containing a φ_A-X-φ_B motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the "CD" domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.

Original language	English (US)
Pages (from-to)	1241-1249
Number of pages	9
Journal	Molecular cell
Volume	9
Issue number	6
DOIs	https://doi.org/10.1016/S1097-2765(02)00525-7
State	Published - 2002

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/S1097-2765(02)00525-7

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title = "Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b",

abstract = "The structures of the MAP kinase p38 in complex with docking site peptides containing a φA-X-φB motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the {"}CD{"} domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.",

author = "Chang, {Chung I.} and Xu, {Bing E.} and Radha Akella and Cobb, {Melanie H.} and Goldsmith, {Elizabeth J.}",

note = "Funding Information: We thank Mischa Machius and Dominika Borek for collecting the data used in this study; the staff at Argonne for beamline assistance; and Sheng Ye for invaluable assistance with crystallographic software packages. We are grateful to Roger Davis, Shengcai Lin, and Eric Olson for providing reagents. This research was supported by the NIH grants DK46993, I1128, and I1243 from the Welch Foundation. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Biological and Environmental Research, under Contract No. W-31-109-ENG-38. ",

year = "2002",

doi = "10.1016/S1097-2765(02)00525-7",

language = "English (US)",

volume = "9",

pages = "1241--1249",

journal = "Molecular cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "6",

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TY - JOUR

T1 - Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b

AU - Chang, Chung I.

AU - Xu, Bing E.

AU - Akella, Radha

AU - Cobb, Melanie H.

AU - Goldsmith, Elizabeth J.

N1 - Funding Information: We thank Mischa Machius and Dominika Borek for collecting the data used in this study; the staff at Argonne for beamline assistance; and Sheng Ye for invaluable assistance with crystallographic software packages. We are grateful to Roger Davis, Shengcai Lin, and Eric Olson for providing reagents. This research was supported by the NIH grants DK46993, I1128, and I1243 from the Welch Foundation. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Biological and Environmental Research, under Contract No. W-31-109-ENG-38.

PY - 2002

Y1 - 2002

N2 - The structures of the MAP kinase p38 in complex with docking site peptides containing a φA-X-φB motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the "CD" domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.

AB - The structures of the MAP kinase p38 in complex with docking site peptides containing a φA-X-φB motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the "CD" domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.

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DO - 10.1016/S1097-2765(02)00525-7

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AN - SCOPUS:0036289349

SN - 1097-2765

VL - 9

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EP - 1249

JO - Molecular cell

JF - Molecular cell

IS - 6

ER -

Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b

Abstract

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